Online Issues

Journal Vol 50 (3)

Cardiovascular Consequences of Sleep-Disordered Breathing: Contribution of Animal Models to Understanding of the Human Disease

Maurice Dematteis, Diane Godin-Ribuot, Claire Arnaud, Christophe Ribuot, Françoise Stanke-Labesque, Jean-Louis Pépin, and Patrick Lévy

All the authors are in the HP2 Laboratory, INSERM ERI17, at the Université Joseph Fourier in Grenoble, France. Maurice Dematteis, MD, PhD, is an associate professor and Diane Godin-Ribuot, PhD, Jean-Louis Pépin, MD, PhD, and Patrick Lévy, MD, PhD, are professors of physiology; Christophe Ribuot, PharmD, PhD, is a professor and Françoise Stanke-Labesque, PharmD, PhD, an associate professor of pharmacology; and Claire Arnaud, PharmD, PhD, is an INSERM researcher. Drs. Dematteis, Lévy, Pépin, and Stanke-Labesque are also at the Centre Hospitalier Universitaire (CHU) Hôpital A. Michallon in Grenoble, in the Laboratoires du Sommeil et d’Explorations Fonctionnelles CardioRespiratoires, and in the Laboratoire de Pharmacologie, respectively.

Address correspondence and reprint requests to Drs. Maurice Dematteis and Patrick Lévy, Laboratoire HP2, Institut Jean Roget, Faculté de Médecine de Grenoble, 38042 Grenoble cedex 9, France or email Maurice.Dematteis@ujf-grenoble.fr and PLévy@chu-grenoble.fr.

Abstract

Sleep-disordered breathing, and particularly the highly prevalent obstructive sleep apnea syndrome, is a multicomponent disorder combining intermittent hypoxia (IH), sleep fragmentation, and obstructed respiratory efforts. It is frequently associated with comorbidities and leads to numerous complications, including cardiovascular consequences that are conditioned by genetic predisposition and environment. The complexity of the disease and the reduced possibilities for patient investigations, especially at the tissue level, have limited progress in the understanding of sleep apnea pathophysiology and in the development of specific treatments. Animal models make it possible to study the causative mechanisms (essentially upper airway dysfunction) and the consequences (cardiovascular, metabolic, and neurological alterations) of nocturnal respiratory events without the confounding factors that occur in humans. Such studies have revealed some of the pathophysiological mechanisms and enabled the recognition of IH as the most important sleep apnea component underlying cardiovascular complications. We review different animal models used to assess detrimental sleep apnea–related cardiovascular consequences: blood pressure elevation, impaired vasoreactivity, structural arterial remodeling leading to atherosclerosis, cardiac remodeling, and myocardial infarction. We also review experimental evidence of beneficial effects of IH. By combining clinical and experimental research, these models will contribute to the understanding of differential patient susceptibility and to the elaboration of prevention strategies and tailored treatments for sleep apnea patients.

Key Words: atherosclerosis; cardiovascular remodeling; hypertension; inflammation; intermittent hypoxia; myocardial infarction; pre-/postconditioning; sleep apnea